Rapid and profound decay of inducible and intact HIV genomes in early-treated Thai children
Marta Massanella, Caroline Dufour, Amélie Pagliuzza, Audrée Lemieux, Corentin Richard, Jintanat Ananworanich, Louise Leyre, Thidarat Jupimai, Supranee Buranapraditkun, Rapisa Nantanee, Julie L. Mitchell, Panadda Sawangsinth, Mark de Souza, Piyarat Suntarattiwong, Suparat Kanjanavanit, Pope Kosalaraksa, Thitiporn Borkird, Witaya Petdachai, Kulkanya Chokephaibulkit, Lydie Trautmann, Rémi Fromentin, Thanyawee Puthanakit, Nicolas Chomont, on behalf of the HIV Netherlands Australia Thailand Research Collaboration 209 and 194 (HIVNAT209 and HIVNAT194) study groups
Marta Massanella, Caroline Dufour, Amélie Pagliuzza, Audrée Lemieux, Corentin Richard, Jintanat Ananworanich, Louise Leyre, Thidarat Jupimai, Supranee Buranapraditkun, Rapisa Nantanee, Julie L. Mitchell, Panadda Sawangsinth, Mark de Souza, Piyarat Suntarattiwong, Suparat Kanjanavanit, Pope Kosalaraksa, Thitiporn Borkird, Witaya Petdachai, Kulkanya Chokephaibulkit, Lydie Trautmann, Rémi Fromentin, Thanyawee Puthanakit, Nicolas Chomont, on behalf of the HIV Netherlands Australia Thailand Research Collaboration 209 and 194 (HIVNAT209 and HIVNAT194) study groups
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Research Article AIDS/HIV Immunology Virology

Rapid and profound decay of inducible and intact HIV genomes in early-treated Thai children

Abstract

Early initiation of antiretroviral therapy (ART) in perinatally HIV-infected children significantly limits the establishment of the viral reservoir. However, the long-term impact of this intervention remains unclear. We measured the frequency of inducible, translation-competent, and replication-competent proviruses in samples from 62 children who initiated ART early and remained virally suppressed for up to 9.9 years. Only a small fraction of HIV genomes produced HIV transcripts, viral proteins, or infectious virions. Accordingly, replication-competent virus was detected in only 11% of the participants. Despite the predominance of naive cells in pediatric blood, most proviruses were detected in memory CD4+ T cells, especially central memory cells. Longitudinal analysis revealed a biphasic decay in HIV DNA: an initial decline followed by long-term stability, which was associated with extensive expansions of infected T cell clones. In contrast, inducible proviruses declined continuously and became undetectable in most children after 5 years. Near full-length sequencing of 1,305 HIV genomes revealed a dramatic reduction in genetically intact proviruses, from pre-ART to after 7 years of ART. Together, these findings suggest that the intact viral reservoir rapidly decays in early-treated children, offering critical insights for pediatric HIV cure strategies.

Authors

Marta Massanella, Caroline Dufour, Amélie Pagliuzza, Audrée Lemieux, Corentin Richard, Jintanat Ananworanich, Louise Leyre, Thidarat Jupimai, Supranee Buranapraditkun, Rapisa Nantanee, Julie L. Mitchell, Panadda Sawangsinth, Mark de Souza, Piyarat Suntarattiwong, Suparat Kanjanavanit, Pope Kosalaraksa, Thitiporn Borkird, Witaya Petdachai, Kulkanya Chokephaibulkit, Lydie Trautmann, Rémi Fromentin, Thanyawee Puthanakit, Nicolas Chomont, on behalf of the HIV Netherlands Australia Thailand Research Collaboration 209 and 194 (HIVNAT209 and HIVNAT194) study groups

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Figure 3

Evolution of the HIV persistence markers and distribution of integrated HIV DNA in CD4+ T cell subsets over time in early-ART-treated Thai children.

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Evolution of the HIV persistence markers and distribution of integrated ...
(A) Changes over time in the frequencies of infected cells in samples from 8 ART-suppressed children were assessed at 2 time points using 4 assays: total HIV DNA, integrated HIV DNA, TILDA, and HIV-Flow. Undetectable measurements are represented as unfilled symbols, and the half of the LOD are plotted. (B) Percentage of CD4+ T cell subsets (naive, central memory [CM], transitional memory [TM], and effector memory [EM]) among total CD4+ T cells in the same 8 early-ART-treated children at the same time points. (C) Frequency of cells harboring integrated HIV DNA in sorted CD4+ T cell subsets from the same individuals. Undetectable measurements are represented as unfilled symbols, and the half of the LOD are plotted. (D) Contribution of each CD4+ T cell subset to the pool of HIV-infected cells from each individual. For panels A–D, each sample is represented by a unique color-coded symbol and unique ID, followed by the number of years on suppressive ART from the first (T1) and second (T2) time point. Data were log10-transformed, and Wilcoxon’s matched pairs signed-rank test was used to compare both time points. (E) Comparison of the contribution of CD4+ T cell subsets to the pool of circulating CD4+ T cells and to the pool of HIV-infected cells, summarized by pie charts displaying the mean proportions across individuals at T1 and T2. Wilcoxon’s matched pairs signed-rank test was used to compare the contribution of each CD4+ T cell subset to the pool of circulating cells with its contribution to the pool of HIV-infected cells.